Furosemide Holds Up to Newer, Stronger Loop Diuretic During HF Hospitalization

CHICAGO — The choice between furosemide and torsemide didn’t matter for longer-term clinical outcomes of hospitalized heart failure patients, according to the comparative effectiveness trial TRANSFORM-HF.

The incidence of all-cause mortality was just over 26% over a median follow-up 17.4 months, or the same 17.0 per 1oo patient-years, for individuals randomly assigned either loop diuretic during their hospital stay (HR 1.02, 95% CI 0.89-1.18), reported Robert Mentz, MD, of Duke University Medical Center in Durham, North Carolina, at the American Heart Association (AHA) annual meeting.

No between-group differences were observed in terms of total subsequent hospitalizations (37.5% with torsemide vs 40.4% with furosemide, RR 0.94, 95% CI 0.84-1.07) or combined deaths and hospitalizations, either (47.3% vs 49.3%, HR 0.92, 95% CI 0.83-1.02).

“We were disappointed at first because we hoped that there would be a significant clinical difference between these two medicines based on prior studies and clinical experience. While we did not see better outcomes with torsemide, these results help inform our ability to take better care of people living with heart failure,” Mentz said in a press release.

“Now that we have an answer in this debate, we encourage health care professionals to redirect time in a more patient-focused way. Rather than focus on one loop diuretic versus the other, we can focus efforts on making sure the appropriate dose of the loop diuretic is prescribed and re-double our efforts on the therapies that improve outcomes for our patients,” he stated.

Furosemide has historically been the most common loop diuretic used for the management of volume in heart failure. It remains preferred due to its familiarity and low cost in clinical practice. Torsemide, a newer but still fairly inexpensive agent, is thought to work better due to more consistent oral bioavailability, a longer duration of action, and other mechanistic effects — but has not been proven to be more effective clinically.

AHA session discussant Biykem Bozkurt, MD, PhD, of Baylor College of Medicine in Houston, said that TRANSFORM-HF investigators may have been too optimistic in trying to show a survival benefit to torsemide when, in recent trials, most heart failure drugs are associated with reduced cardiovascular death and heart failure hospitalizations specifically.

Moreover, Mentz’s group included the historically hard-to-treat group of people with preserved ejection fraction, and the overall cohort was subject to expanding guideline-directed medical therapy in the background over the course of the study, Bozkurt noted.

As such, she concluded, “TRANSFORM likely will not alter practice. Clinicians likely will continue to use torsemide according to their discretion, especially when better bioavailability and diuretic potency are desired, particularly in heart failure patients with diuretic resistance, significant congestion, and chronic kidney disease.”

The trial was conducted at 60 U.S. sites and began recruitment in 2018.

Mentz and colleagues had 2,859 people (mean age 65, fewer than 40% women, 33% Black) randomized to one of the two study loop diuretics. The proportion with newly diagnosed heart failure was 30%.

Mentz highlighted the pragmatic nature of the trial, which featured broad eligibility criteria and a streamlined study protocol embedded within routine care. There were no in-person study visits, and investigators instead relied on telephone follow-up and national death records.

Prior to admission, 67% of participants were on a loop diuretic, mostly furosemide, with a total daily dose of 66 mg furosemide equivalent. Total daily dose rose to about 80 mg furosemide equivalent at discharge, after local clinicians had been given room to decide the diuretic dosing for each patient.

As TRANSFORM-HF was conducted open-label, it was possible that bias may have prompted medication switches during the study. Cross-over and diuretic discontinuation occurred among both furosemide and torsemide users.

Nevertheless, Mentz reported that the main findings persisted in on-treatment analysis of people who were taking their assigned medication at discharge and 30 days.

As the trial was conducted during the pandemic, all-cause findings may have also been affected by the COVID-19. Furthermore, the trial did not assess decongestion or adverse events such as worsening renal function, electrolyte abnormalities, or non-hospitalization events.